title: Interaction of selenite and tellurite with thiol-dependent redox enzymes: Kinetics and mitochondrial implications.
abstract: The interactions of selenite and tellurite with cytosolic and mitochondrial thioredoxin reductases (TrxR1 and TrxR2) and glutathione reductases (GR) from yeast and mammalian sources were explored. Both TrxR1 and TrxR2 act as selenite and tellurite reductases. Kinetic treatment shows that selenite has a greater affinity than tellurite with both TrxR1 and TrxR2. Considering both k(cat) and K(m), selenite shows a better catalytic efficiency than tellurite with TrxR1, whereas with TrxR2, the catalytic efficiency is similar for both chalcogens. Tellurite is a good substrate for GR, whereas selenite is almost completely ineffective. Selenite or tellurite determine a large mitochondrial permeability transition associated with thiol group oxidation. However, with increasing concentrations of both chalcogens, only about 25% of total thiols are oxidized. In isolated mitochondria, selenite or tellurite per se does not stimulate H₂O₂ production, which, however, is increased by the presence of auranofin. They also determine a large oxidation of mitochondrial pyridine nucleotides. In ovarian cancer cells both chalcogens decrease the mitochondrial membrane potential. These results indicate that selenite and tellurite, interacting with the thiol-dependent enzymes, alter the balance connecting pyridine nucleotides and thiol redox state, consequently leading to mitochondrial and cellular alterations essentially referable to a disulfide stress.
authors.affiliation: Department of Biological Chemistry, University of Padova, Padova, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Rigobello
authors.forename: Alessandra
authors.initials: A
authors.lastname: Folda
authors.forename: Anna
authors.initials: A
authors.lastname: Citta
authors.forename: Guido
authors.initials: G
authors.lastname: Scutari
authors.forename: Valentina
authors.initials: V
authors.lastname: Gandin
authors.forename: Aristi Potamitou
authors.initials: AP
authors.lastname: Fernandes
authors.forename: Anna-Klara
authors.initials: AK
authors.lastname: Rundlöf
authors.forename: Cristina
authors.initials: C
authors.lastname: Marzano
authors.forename: Mikael
authors.initials: M
authors.lastname: Björnstedt
authors.forename: Alberto
authors.initials: A
authors.lastname: Bindoli
mesh_terms: D000818:Animals; D001310:Auranofin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D005260:Female; D005980:Glutathione Reductase / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D011725:Pyridines / Q000378:metabolism; D051381:Rats; D018038:Sodium Selenite / Q000737:chemistry / Q000494:pharmacology*; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013691:Tellurium / Q000737:chemistry / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry / Q000378:metabolism*; D015003:Yeasts
chemical_list: D011725:Pyridines; D013438:Sulfhydryl Compounds; D001310:Auranofin; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase; D018038:Sodium Selenite; C026660:tellurous acid; D013691:Tellurium